OCA at 12:04, 1 February 2024

OCA — Thu, 01 Feb 2024 12:04:44 GMT

←Older revision		Revision as of 12:04, 1 February 2024
Line 1:		Line 1:

-	====	+	==Crystal structure of RXR alpha LBD in complexes with palmitic acid and GRIP-1 peptide==
-	<StructureSection load='7a77' size='340' side='right'caption='[[7a77]]' scene=''>	+	<StructureSection load='7a77' size='340' side='right'caption='[[7a77]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a77]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A77 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7a77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a77 OCA], [~~http~~://pdbe.org/7a77 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7a77 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7a77 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7a77 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7a77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a77 OCA], [https://pdbe.org/7a77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a77 RCSB], [https://www.ebi.ac.uk/pdbsum/7a77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a77 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RXRA_HUMAN RXRA_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The retinoid X receptor (RXR) is a ligand-sensing transcription factor acting mainly as a universal heterodimer partner for other nuclear receptors. Despite presenting as a potential therapeutic target for cancer and neurodegeneration, adverse effects typically observed for RXR agonists, likely due to the lack of isoform selectivity, limit chemotherapeutic application of currently available RXR ligands. The three human RXR isoforms exhibit different expression patterns; however, they share high sequence similarity, presenting a major obstacle toward the development of subtype-selective ligands. Here, we report the discovery of the saturated fatty acid, palmitic acid, as an RXR ligand and disclose a uniform set of crystal structures of all three RXR isoforms in an active conformation induced by palmitic acid. A structural comparison revealed subtle differences among the RXR subtypes. We also observed an ability of palmitic acid as well as myristic acid and stearic acid to induce recruitment of steroid receptor co-activator 1 to the RXR ligand-binding domain with low micromolar potencies. With the high, millimolar endogenous concentrations of these highly abundant lipids, our results suggest their potential involvement in RXR signaling.
		+
		+	Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms.,Chaikuad A, Pollinger J, Ruhl M, Ni X, Kilu W, Heering J, Merk D Int J Mol Sci. 2020 Nov 11;21(22):8457. doi: 10.3390/ijms21228457. PMID:33187070<ref>PMID:33187070</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7a77" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Retinoid X receptor 3D structures\|Retinoid X receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Chaikuad A]]
		+	[[Category: Knapp S]]
		+	[[Category: Merk D]]

OCA at 08:16, 21 October 2020

OCA — Wed, 21 Oct 2020 08:16:55 GMT

←Older revision		Revision as of 08:16, 21 October 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7a77 ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7a77' size='340' side='right'caption='[[7a77]]' scene=''>
-	~~Authors~~: ~~Chaikuad, A~~.~~, Merk, D~~.~~, Knapp, S~~.~~, Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal~~ structure ~~of RXR alpha LBD in complexes with palmitic acid and GRIP-1 peptide~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7a77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a77 OCA], [http://pdbe.org/7a77 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7a77 RCSB], [http://www.ebi.ac.uk/pdbsum/7a77 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7a77 ProSAT]</span></td></tr>
-	[~~[Category~~: ~~Unreleased Structures]~~]	+	</table>
-	[[~~Category~~: ~~Chaikuad~~, A]]	+	__TOC__
-	[~~[Category~~: ~~Merk, D~~]]	+	</StructureSection>
-	[[Category: ~~Knapp, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Z-disk]]

OCA: Protected "7a77" [edit=sysop:move=sysop]

OCA — Wed, 02 Sep 2020 05:07:33 GMT

Protected "7a77" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:07, 2 September 2020

OCA: New page: '''Unreleased structure''' The entry 7a77 is ON HOLD Authors: Chaikuad, A., Merk, D., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of RXR alpha LBD in...

OCA — Wed, 02 Sep 2020 05:07:32 GMT

New page: '''Unreleased structure''' The entry 7a77 is ON HOLD Authors: Chaikuad, A., Merk, D., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of RXR alpha LBD in...

New page

'''Unreleased structure'''

The entry 7a77 is ON HOLD

Authors: Chaikuad, A., Merk, D., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of RXR alpha LBD in complexes with palmitic acid and GRIP-1 peptide
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Merk, D]]
[[Category: Knapp, S]]
[[Category: Structural Genomics Consortium (Sgc)]]

7a77 - Revision history

OCA at 12:04, 1 February 2024

OCA at 08:16, 21 October 2020

OCA: Protected "7a77" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7a77 is ON HOLD Authors: Chaikuad, A., Merk, D., Knapp, S., Structural Genomics Consortium (SGC) Description: Crystal structure of RXR alpha LBD in...